Tumor immunity to murine plasma‐cell tumors. VIII. Immunosuppression of the generation of cytotoxic T cells by murine plasma‐cell tumor lines

Abstract

Previous studies have clearly established that murine plasmacytomas suppress B-cell responses, but no effects on T-cell responses have been noted by most investigators. However, in our investigation of the tumor-associated antigens of plasmacytomas, we have found that immunosuppression plays an important role in the complex interaction between host immune T cells and tumor cells. In these investigations, varying the number of plasmacytoma cells added to in vitro induction systems separated two different effects which these cells had on the generation of cytotoxic T cells. On the one hand, when appropriate numbers were present, tumor cells acted as immunogens and stimulated the generation of specific killer cells against tumor-associated antigen or alloantigen which they expressed. In contrast, greater numbers of tumor cells exerted a profound inhibitory effect on the generation of cytotoxic activity when cells inactivated with irradiation were used. Mitomycin-C inactivation of plasmacytoma cells abrogated this inhibitory activity. In further experiments, MPC-II cells that had been inactivated with Mitomycin C were able to prime T cells in vivo, whereas priming by live tumor cells could not be detected in the same situation. It is suggested that immunosuppression by the live tumor cells may account for their inability to prime T cells in vivo. These results indicate that immunosuppression by plasmacytomas may be one of the important variables which influence the generation of cytotoxic T cells against tumor-associated antigens both in vivo and in vitro.

Cure of mice bearing a late-stage, highly metastatic, drug-resistant tumor by adoptive chemoimmunotherapy

“…Accordingly, the metastatic tumor cells may not be sufficiently immunogenic (as a result of too few cells or loss of some surface antigens [29]) or may exert some immunosuppressive activity [6,10]. Still, from our findings it is clear that even in the presence of potential immunosuppressive activity of RPC-5 tumor metastases, culture of these TISpC with inactivated RPC-5 tumor cells and PEG renders the spleen cells highly effective in ACIT.…”

Paired epstein‐barr virus‐carrying lymphoma and lymphoblastoid cell lines Burkitt's lymphoma patients: Comparative sensitivity to non‐specific and to allo‐specific cytotoxic responses in vitro

“…In other cases, however, preliminary observations suggest that several of the BL lines may be able to actively suppress antigen-specific cytotoxic T-cell responses in vitro (D.J. Moss unpub-lished observations) in a manner perhaps akin to that recently reported for mouse plasmacytoma cell lines (Giorgi and Warner, 1983). It remains to be seen, therefore, to what extent the immunogenicity of BL cell lines in this in vitro situation directly reflects quantitative levels of HLA antigen expression on the cell surface.…”

Frequency of Murine Cytotoxic T Cell Precursors Reactive to Plasma Cell Tumour‐associated Antigens as Compared to Major Histocompatibility Antigens

“…Mitomycin C was used to inactivate the tumour ceils, both because stimulator tumour cells prepared in this way are more immunogenic than irradiated cells (Burton el al., 1975), and because irradiated tumour cells appear to be immunosuppressive of in vitro T cell responses, in tbat they can suppress the in vitro allograft reaction (Giorgi and Warner, 1983).…”

“…Tbe tissue culture medium (TCM) used, the preparation of viable erythrocyte free spleen cell suspensions, the procedure used to test foetal calf serum and the techniques used to inactivate cells with mitomycin C or irradiation have all been described previously (Burton et al, 1975). Mitomycin C was used to inactivate the tumour ceils, both because stimulator tumour cells prepared in this way are more immunogenic than irradiated cells (Burton el al., 1975), and because irradiated tumour cells appear to be immunosuppressive of in vitro T cell responses, in tbat they can suppress the in vitro allograft reaction (Giorgi and Warner, 1983).…”